Protonated (S)-prolinamide derivatives—water compatible organocatalysts for direct asymmetric aldol reaction

Protonated chiral (S)-prolinamide derivatives have been developed as water compatible highly efficient organocatalysts for a direct enantioselective aldol reaction. A simple protonated (S)-prolinamide organocatalyst prepared from l-proline and 3-nitroaniline catalyzes the aldol reaction of unmodified ketones and a variety of aromatic aldehydes yielding aldol product in high yield with enantioselectivities of up to 98% and diastereoselectivity of up to >99:1.

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(S)-2-(4′-Fluorophenylcarbamoyl)pyrrolidinium bromideC11H14N2OFBr[α]D20=-38.8 (c 1.0, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-2-(4′-Chlorophenylcarbamoyl)pyrrolidinium bromideC11H14N2OClBr[α]D20=-36.4 (c 1.0, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-2-(4′-Bromophenylcarbamoyl)pyrrolidinium bromideC11H14N2OBr2[α]D20=-37.4 (c 1.0, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-2-(4′-Nitrophenylcarbamoyl)pyrrolidinium bromideC11H14N3O3Br[α]D20=-36.3 (c 0.71, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-2-(3′-Nitrophenylcarbamoyl)pyrrolidinium bromideC11H14N3O3Br[α]D20=-38.1 (c 0.94, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-2-(2′-Nitrophenylcarbamoyl)pyrrolidinium bromideC11H14N3O3Br[α]D20=-29.7 (c 0.21, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-2-(1′-Naphthmethylcarbamoyl)pyrrolidinium bromideC16H19N2OBr[α]D20=-22.6 (c 0.41, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-2-(1′-Naphthmethylcarbamoyl)pyrrolidinium bromideC16H19N2OBr[α]D20=-22.4 (c 0.49, MeOH)Source of chirality: l-prolineAbsolute configuration: (S)